AI Article Synopsis
- The Hippo/MST2 pathway is a crucial signaling system that regulates organ size in fruit flies and has expanded functions in mammals, particularly in cancer biology.
- Disruptions in the MST2 pathway are linked to tumor development through their impact on cell processes like apoptosis and the cell cycle, and they interact with other signaling pathways.
- This review focuses on how cancer-related changes, like mutations in RAS and PI3K/Akt, affect MST2 activity, along with mechanisms such as protein-protein interactions and gene silencing that lead to its down-regulation in cancer.
Article Abstract
The Hippo/MST2 (mammalian sterile 20-like kinase 2) pathway is a signalling cascade evolutionarily conserved in its structure. Originally described in Drosophila melanogaster as a regulator of organ size, this pathway has greater functions in mammals. Disturbance of mammalian MST2 pathway is associated with tumorigenesis by affecting apoptosis, cell cycle and polarity. In addition, this pathway has been shown to cross-talk with mitogenic pathways at multiple levels. In the present mini-review, we discuss our contribution highlighting the regulation of MST2 signalling by frequently observed oncogenic perturbations affecting mitogenic pathways. In particular, we review the role of RAS isoforms and PI3K (phosphoinositide 3-kinase)/Akt in the regulation of MST2 activity by phosphorylation. We also put the emphasis on RAF-induced control of MST2 signalling by protein-protein interactions. Finally, we recapitulate some of the direct mechanisms, such as ubiquitin-dependent degradation or gene silencing by promoter hypermethylation, involved in MST2 pathway component down-regulation in cancers.
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| http://dx.doi.org/10.1042/BST20140030 | DOI Listing |
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